It's a dogma taught in every introductory biology class: Proteins are composed of combinations of 20 different amino acids, arranged into diverse sequences like words.
The novel method uses sets of four RNA nucleotides--rather than the natural three--to encode new, synthetic building blocks into proteinsIt's a dogma taught in every introductory biology class: Proteins are composed of combinations of 20 different amino acids, arranged into diverse sequences like words.
"Our goal is to develop proteins with tailored functions for applications in fields spanning bioengineering to drug discovery," says senior author Ahmed Badran, PhD, an assistant professor of chemistry at Scripps Research."Being able to incorporate non-canonical amino acids into proteins with this new method gets us closer to that goal."
"Creating free codons by whole genome recoding can be a powerful strategy, but it can also be a challenging undertaking since it requires considerable resources to build new genomes," says Badran."For the organism itself, it can be difficult to predict how such codon changes influence genome stability and host protein production."
Badran's group then tested whether they could alter the sequence of a single gene so that it had a new four-nucleotide codon that would be correctly used by the cell. The method worked: When the researchers surrounded a target site with three-letter, frequently used codons and maintained sufficient levels of the four-nucleotide tRNA, the cell incorporated any new amino acid that was attached to the corresponding four-letter tRNA.
"Our results suggest that one can now easily and effectively incorporate non-canonical amino acids at diverse sites in a wide array of proteins," says Badran."We're excited about these possibilities for our ongoing work and to provide this capability to the broader community."
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